BACKGROUND: The mechanisms of thoracic aortic aneurysm (TAA) formation are poorly understood, mainly due to the lack of a useful and reproducible model. Accordingly, the goal of this study was to test the hypothesis that abluminal calcium chloride (CaCl(2)) application could create TAAs in the mouse. MATERIALS AND METHODS: Adult 129/SvE mice (n = 8) were anesthetized and their thoracic aortas exposed via left thoracotomy. CaCl(2) (0.5M) was applied to the distal descending thoracic aorta for 15 min followed by chest closure. At 4 weeks, the perfusion-fixed aorta was harvested from the root to the renal arteries. Diameter measurements were made using confocal microscopy, and wall thickness was measured from hematoxylin and eosin-stained sections. RESULTS: The control (n = 15) distal descending thoracic aortic diameter was 0.60 +/- 0.04 mm and increased by 25% (0.76 +/- 0.06 mm, P < 0.05) following CaCl(2) treatment. Control aortic wall thickness was 48 +/- 9 mum and decreased by 47% in corresponding CaCl(2)-exposed segments (25 +/- 8 mum, P < 0.05). The diameter and wall thickness of the ascending aorta (used as an internal control) were not significantly different between groups. Picrosirius red staining of the TAA showed adventitial collagen breakdown and disruption of lamellar organization. CONCLUSIONS: We conclude that abluminal application of CaCl(2) to the thoracic aorta reliably produces dilation, wall-thinning, and disruption of mural architecture, the hallmark signs of aneurysm formation. To our knowledge, these findings describe for the first time the generation of a reproducible model of isolated TAA formation in a murine system.
BACKGROUND: The mechanisms of thoracic aortic aneurysm (TAA) formation are poorly understood, mainly due to the lack of a useful and reproducible model. Accordingly, the goal of this study was to test the hypothesis that abluminal calcium chloride (CaCl(2)) application could create TAAs in the mouse. MATERIALS AND METHODS: Adult 129/SvE mice (n = 8) were anesthetized and their thoracic aortas exposed via left thoracotomy. CaCl(2) (0.5M) was applied to the distal descending thoracic aorta for 15 min followed by chest closure. At 4 weeks, the perfusion-fixed aorta was harvested from the root to the renal arteries. Diameter measurements were made using confocal microscopy, and wall thickness was measured from hematoxylin and eosin-stained sections. RESULTS: The control (n = 15) distal descending thoracic aortic diameter was 0.60 +/- 0.04 mm and increased by 25% (0.76 +/- 0.06 mm, P < 0.05) following CaCl(2) treatment. Control aortic wall thickness was 48 +/- 9 mum and decreased by 47% in corresponding CaCl(2)-exposed segments (25 +/- 8 mum, P < 0.05). The diameter and wall thickness of the ascending aorta (used as an internal control) were not significantly different between groups. Picrosirius red staining of the TAA showed adventitial collagen breakdown and disruption of lamellar organization. CONCLUSIONS: We conclude that abluminal application of CaCl(2) to the thoracic aorta reliably produces dilation, wall-thinning, and disruption of mural architecture, the hallmark signs of aneurysm formation. To our knowledge, these findings describe for the first time the generation of a reproducible model of isolated TAA formation in a murine system.
Authors: Jeffrey A Jones; Juozas A Zavadzkas; Eileen I Chang; Nina Sheats; Christine Koval; Robert E Stroud; Francis G Spinale; John S Ikonomidis Journal: J Thorac Cardiovasc Surg Date: 2010-03-09 Impact factor: 5.209
Authors: Jeffrey A Jones; John R Barbour; Abigail S Lowry; Shenikqua Bouges; Christy Beck; David M McClister; Rupak Mukherjee; John S Ikonomidis Journal: J Vasc Surg Date: 2006-12 Impact factor: 4.268
Authors: Jeffrey A Jones; John R Barbour; Robert E Stroud; Shenikqua Bouges; Shelly L Stephens; Francis G Spinale; John S Ikonomidis Journal: J Vasc Res Date: 2008-04-23 Impact factor: 1.934
Authors: William F Johnston; Morgan Salmon; Nicolas H Pope; Akshaya Meher; Gang Su; Matthew L Stone; Guanyi Lu; Gary K Owens; Gilbert R Upchurch; Gorav Ailawadi Journal: Circulation Date: 2014-09-09 Impact factor: 29.690
Authors: Shaina R Eckhouse; Christina B Logdon; J Marshall Oelsen; Risha K Patel; Allison D Rice; Robert E Stroud; W Benjamin Wince; Rupak Mukherjee; Francis G Spinale; John S Ikonomidis; Jeffrey A Jones Journal: Circulation Date: 2013-09-10 Impact factor: 29.690